Journal of the College of Psychiatric and Neurologic Pharmacists
The College of Psychiatric and Neurologic Pharmacists (CPNP) has established an online Journal designed to update and educate readers. If you are interested in submitting an article for consideration, please EMail Rob Dufresne, PhD, BCPP, Editor to discuss your submission for peer-review and posting. Residents and CPNP members are encouraged to contribute to and support our scholarly journal with case reports, literature reviews, opinions, research reports, and systematic article reviews (Journal Club).
The Procedure for article review, reviewer's form, and members of the peer review panel are available for viewing.
Comparison of Antipsychotic Polytherapy Use in Community and Academic Hospitals
Jessica L. Gören, PharmD, BCPP
Clinical Pharmacist Specialist
Cambridge Health Alliance
120 Beacon Street, Suite 202
Somerville, MA 02143
Introduction:
Rates of antipsychotic polytherapy have risen dramatically over several decades and have been reported in all treatment settings in many different countries. In addition, rigorously controlled studies have found antipsychotic polytherapy increases side effects and cost without improving primary outcome measures. Improvements on secondary measures have been reported by a few studies. Without supporting data, the increasing rates of antipsychotic polytherapy are coming under increased scrutiny.
Based on unique pharmacologic profiles, the combined use of a second generation antipsychotics (SGA) with another SGA or first generation antipsychotics (FGA) may represent the rational use of antipsychotic polytherapy. However, this theoretically intriguing concept is not supported by the medical literature. Randomized controlled clinical trials have not consistently shown antipsychotic polytherapy to be more effective than monotherapy. Of the ten randomized controlled trials, two reported improvement in primary outcome measures with antipsychotic polytherapy , one reported improvement with monotherapy, and seven found no differences between groups. Mixed results have been obtained in studies of polytherapy on secondary outcome measures, with six reporting improvements and onereporting worsening of symptoms. Polytherapy exposes patients to both extrapyramidal side effects (EPS) from the FGAs and metabolic side effects associated with the SGAs. Use of two SGAs has been shown to increase side effects including EPS, thus eliminating one of the main advantages of SGAs. Multiple studies have also found increased rates of side effects such as hyperprolactinemia and sedation with a variety of antipsychotic combinations.In practice, combining unique pharmacologic mechanisms of action appears to increase the side effect burden of antipsychotics without providing synergistic efficacy.
Currently, evidence is lacking due to the limited number of antipsychotic combinations reported. The trials reporting positive effects on secondary outcome measures either address augmentation of clozapine or antipsychotics medications not currently available in the US. The majority of data, positive or negative, address clozapine augmentation. However, this combination accounts for only a small percentage of antipsychotic polytherapy use. Combinations of non-clozapine SGAs together or with FGAs are the predominate forms of antipsychotic polytherapy.
Differing definitions of polytherapy (inclusion or exclusion of as need antipsychotics, acceptable justifications, length of time of concomitant antipsychotic prescription) have hampered our ability to compare polytherapy between studies and treatment facilities. Regardless, it would be beneficial to identify areas of focus to curb prescribing of antipsychotic polytherapy. Cambridge Health Alliance represents a unique opportunity to compare rates of antipsychotic polytherapy across treatment settings due to inclusion of both academic and community hospitals. Given limited resources, we sought to identify which hospitals within the Cambridge Health Alliance were most in need of interventions to address antipsychotic polytherapy prescribing practices.
Psychiatric Advance Directives and Board Certified Psychiatric Pharmacists: An Opportunity for Patient Empowerment
Nancy C. Brahm, PharmD, MS, BCPP, CGP
Clinical Associate Professor, Department of Pharmacy
University of Oklahoma College of Pharmacy
Julie C. Kissack, PharmD, BCPP
Professor and Chair, Pharmacy Practice
Harding University College of Pharmacy
Introduction:
In times of psychiatric crisis, the most vulnerable population, those with severe, often debilitating, mental illnesses, may be least able to advocate for their care and make their treatment preferences known. The psychiatric advance directive (PAD) is a transportable vehicle used to empower persons with a psychiatric disability to advocate for their treatment desires even when incapacitated during an acute exacerbation.
Psychiatric Advance Directives, also called Mental Health Advance Directives in states that recognize them (Figure 1), are legal tools developed prior to a psychiatric crisis, to allow individuals to clearly identify preferences for future mental health treatment. At the time when this document is developed, the individual is competent, autonomous, and able to articulate their wishes.1 The PAD generally contains patient treatment preferences, medical and treatment histories, comorbid conditions of importance for the treating physician or facility, emergency contact information, and history of medication treatment and side effects that may help the treating clinician make informed treatment decisions for the current admission.2 The document may also include identification of a designated healthcare agent charged with communicating the wishes of the person in crisis.3 Further information about PADs can be found at the National Resource Center on Psychiatric Advance Directives at www.nrc-pad.org. Once the PAD is created it can be stored electronically at an internet site. The Living Will Registry is a repository that contains all types of advance directives, including PADs which can be stored for a onetime fee of $125.00. Use of this registry also includes provisions for protection of healthcare information. Information about this registry is available on the internet at www.uslivingwillregistry.com. On an annual basis, a person storing advance directives at this website is notified that the document should be reviewed and updated as desired.
Not all states recognize PADs and each state may have individual rules about how to file the documents. In those states with advance directive provisions, limited knowledge about the document and difficulties explaining its use in the inpatient setting were identified as barriers to effective use of the PAD.1 Furthermore, in these states clinicians educated about PADs and associated legal implications viewed the use of an advance directive more favorably than counterparts who did not have the education.3 Other barriers to PAD use could include lack of resources (e.g. unable to access form, inability to use a computer, lack of funds for lifetime filing fee for the Living Will Registry), failing to file the PAD in a central location or communicate its existence or incorrectly executing the document. In addition, the definition of ‘incapacity’ varies by state and may contribute to confusion about when and if the PAD instructions should be implemented during an acute exacerbation. Concern about whether or not PAD directions can be overridden, in what circumstances, and the legal liability of such action by the clinician also prevents effective use of the PAD.4
This article will review select literature surrounding the utility of PADs, clinician perspectives related to the use of one, including clinician attitudes on their use, and the results of facilitation in completing a PAD. Board certified psychiatric pharmacists (BCPP) practice in a variety of healthcare environments and actively participate in patient care. BCPPs often develop a unique partnership with the person suffering from a mental illness to enhance the person’s ability to advocate for the best care for the individual. These qualifications and background of the BCPP may provide an opportunity to facilitate development and completion of a PAD prior to need.
A Case of Metoclopramide-Mediated Hyperprolactinemia
in an Intellectually Disabled Adult Woman
Nancy Brahm, PharmD, MS, BCPP 1; Robert C. Brown, M.D. 2
Introduction:
Elevated prolactin levels may be due to a variety of causes which include physiological factors, such as stress or lactation, prolactinomas, hypothalamic diseases, endocrine disorders, and medication.1 Medications frequently associated with elevated prolactin levels include antidepressants, antipsychotics, antihypertensive agents, estrogens, and peripheral dopamine antagonists.1
The extent to which medication-associated hyperprolactinemia occurs has not been identified for all populations but has been identified in those diagnosed with psychosis, including schizophrenia. The literature for this population found moderate to severe sexual dysfunction, a frequently reported side effect associated with elevated prolactin levels. Sexual dysfunction was reported by 54% of men diagnosed with schizophrenia receiving antipsychotics and menstrual changes by 91% of the women in this population.2 The extent to which this occurs in the intellectually disabled population has not been extensively reported.
Antipsychotic Polytherapy in a State Medicaid Program from 1990 to 2001
Ryan M. Carnahan, Pharm.D., M.S. 1; Brian C. Lund, Pharm.D., M.S 2; Paul J. Perry, Ph.D. 3,4; Elizabeth A. Chrischilles, Ph.D. 5; Michael Flaum, M.D. 3
Submitted 3/5/2007; Accepted 4/1/2007. Peer Reviewed by Two Reviewers.
Background:
Evidence supporting the use of antipsychotic polytherapy, i.e. the concurrent use of two
or more antipsychotics, is extremely limited.
Methods:
Study Design: Multi-year descriptive study
Subjects: Iowa Medicaid beneficiaries 18-64 years of age receiving prescription drug
coverage from 1989 to 2001.
Primary Measures:
The prevalence of antipsychotic use and antipsychotic polytherapy
on January 1st of each year, stratified by the type of medication and type of polytherapy.
Results:
The proportion of antipsychotic users receiving polytherapy initially decreased, from
10.0% in 1990 to 7.5% in 1994. The prevalence of polytherapy then increased
consistently, reaching its maximum at 15.4% of antipsychotic users in 2001. Atypical
antipsychotic polytherapy, i.e. the concurrent use of two or more atypical antipsychotics,
first appeared in 1995 and increased each year after to 5.4% of antipsychotic users, or
35% of polytherapy, in 2001. The point prevalence of antipsychotic use among Medicaid
beneficiaries approximately doubled, from 3,522 users (6.4%) in 1990 to 6,810 (11.6%)
in 2001, magnifying the financial implications of the increase in polytherapy.
Conclusions:
Antipsychotic polytherapy use increased substantially in this population between 1995
and 2001. As antipsychotic polytherapy becomes more common, it is vital that its safety,
efficacy, and cost-effectiveness be thoroughly assessed.
Introduction:
Atypical antipsychotics have rapidly replaced conventional agents as first-line
pharmacologic treatments for psychotic disorders. These drugs may represent an
important advance in therapy for mental illnesses, due to a reduced risk of extrapyramidal
side effects (EPS) and possible advantages in efficacy compared to conventional agents.
However, their high cost has placed an enormous financial burden on many health care
systems and payers, including government-funded programs such as Medicaid. While
atypical antipsychotic monotherapy is expensive, the concurrent use of two or more
atypical antipsychotics in the same patient is even more so. Treatment with two atypical
antipsychotics may also increase the risk of adverse events, including EPS, compared to
monotherapy. Combining a conventional with an atypical antipsychotic is less
concerning from a cost perspective, but likely increases the risk of EPS and tardive
dyskinesia. The conventional antipsychotic may override the atypical properties of the
more expensive agent by blocking D2 receptors more completely and at locations in the
brain where such blockade is undesirable, resulting in a risk of EPS and tardive
dyskinesia similar to that of the conventional agent, or even worse due to the additional
blockade by the atypical. There are also unanswered questions about the metabolic
risks of combining antipsychotics. Careful consideration must be given to the impact of
dose and co-prescribed medications on the adverse effects of atypical antipsychotics if
the full potential of their benefits is to be recognized such that they are worth the extra
monetary cost.
Conclusive evidence supporting the efficacy or safety of antipsychotic polytherapy, i.e.
the use of two or more antipsychotics concurrently in the same patient, is practically nonexistent. Placebo-controlled studies of antipsychotic polytherapy have been limited to
the augmentation of clozapine with conventional antipsychotics or risperidone. Results have been inconsistent, with some studies suggesting slightly improved efficacy or worsened adverse effects and others not. Adverse effects with combination treatment in these trials have included elevated prolactin, clinically significant increases in fasting blood glucose, memory deficits, akathisia, and others. Despite the high cost and limited supporting evidence, antipsychotic polytherapy prescribing appears to be increasing. However, the extent of this increase is not well-documented. Therefore, the purpose of this study was to describe antipsychotic prescribing trends in clinical practice over time, with a focus on antipsychotic polytherapy.
Antidepressant-Associated Sexual Dysfunction: A Review
Janice Worsham, Pharm.D., Jeffrey R. Bishop, Pharm.D.,M.S., BCPP, Vicki L. Ellingrod, Pharm.D., BCPP
Submitted 9/18/2006; Accepted 1/16/2007. Peer Reviewed by two reviewers.
Sexual dysfunction has been reported to occur in approximately 30-70% of patients receiving antidepressant medications. The highest incidence of sexual dysfunction is seen primarily in patients receiving serotonin reuptake inhibitors (SSRIs) where up to 50-70% of these patients have been shown to have difficulties in sexual functioning. The occurrence of medication-associated sexual dysfunction increases the likelihood of medication non-compliance (or adherence) in patients, which may contribute to untreated depression and/or disease relapse. The goal of this review is to summarize and evaluate the current literature on the occurrence of antidepressant-associated sexual dysfunction as well as to assess the treatment options available for this side-effect.
Case Report: Aripiprazole for the Treatment Resistant Obsessive Compulsive Disorder
Jehan Marino, Pharm.D., Cynthia A Mascarenas, Pharm.D. MS, BCPP, Stephen R. Saklad, Pharm.D. BCPP, Joseph A Simpson, MD
Submitted 10/13/2006; Accepted 1/12/2007. Peer Reviewed by two reviewers.
Evidence for augmentation with atypical antipsychotics for treatment-resistant obsessive compulsive disorder (OCD) is limited. Published data is restricted to open label studies and few small double-blinded studies, mainly with risperidone, olanzapine and quetiapine.1 There is one open-label study with aripiprazole in patients who were not receiving pharmacotherapy for OCD.2 This is a report of the first known case of aripiprazole used as augmentation for treatment-resistant obsessive compulsive disorder.
Venlafaxine Usage Resulted in a False Positive Immunoassay for Phencyclidine
Nancy C. Brahm, PharmD, MS, BCPP, Robert C. Brown, MD
Submitted 9/22/2005; Accepted 9/13/2006. Peer reviewed by 2 reviewers.
Emergency room physicians, particularly in rural settings, may experience resource limitations, one of which may include follow-up verification of initial urine drug screen results. In this setting, versus the legal setting, confirming the results prior to clinical management or therapy initiation may not be possible. As our case demonstrates, venlafaxine may cause a false positive PCP assay irrespective of concentration or reagent. Increased awareness of this potential effect by all healthcare providers is encouraged, particularly when interpreting urine drug assay results on admissions of highly agitated developmentally disabled persons who may have speech articulation difficulties and/or staff unfamiliar with the patient.
No Significant QTc Interval Change in a Case of Intentional Ziprasidone Overdose
Nancy C. Brahm, PharmD, MS, BCPP and Shaun S. Chastka, RPh, MBA
Submitted 04/15/2005; Accepted 07/06/2005. Peer Reviewed by two reviewers.
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Bipolar Disorder in an Individual with Severe Developmental Disability: A Case Report
Jerry McKee Pharm.D. M.S., BCPP, Jennifer Lombard M.A., Steve Mahorney M.D., Roger Jensen M.D.
JCPNP 2004;3(4). Copyright 2004 CPNP. Submitted 01/07/2004; Accepted 11/02/2004. Peer Reviewed by two reviewers.
Due to unique diagnostic and treatment issues, many distinctive clinical situations are encountered in treating psychiatric disorders in those with severe-profound developmental disability and comorbid psychopathology. This report reviews the effects of polypharmacotherapy on the measurable behavioral symptoms displayed by a person with severe mental retardation and an eventual diagnosis of rapid cycling bipolar disorder. The limited verbal skills entailed in this population require a different approach to diagnosis due to lack of useful verbal information exchange. Other obstacles encountered in arriving at a diagnosis and developing an effective treatment plan, including the matter of diagnostic overshadowing, are reviewed.
In the present case, clinically significant improvements in rates of measured behaviors including sleep patterns were observed after the discontinuation of paroxetine and mesoridazine, followed by the initiation of a lithium, olanzapine, and divalproex medication regimen. The patients observed quality of life and functional ability improved with improved mood stability, subsequent to the above noted changes.
Conclusions: The importance of reviewing the current medication regimen as a potential contributor to the presenting problem is imperative. A detailed psychopharmacologic medication history is critical to facilitate sound treatment decisions. The importance of clinical perseverance via a well organized, carefully planned treatment approach is of vital importance.
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Conventional Antipsychotic and Clozapine-Induced Urinary Incontinence
Nancy Clark, PharmD, BCPP
JCPNP 2003;2(2). Copyright 2003 CPNP. Submitted 10/17/2002; Accepted 01/13/2003. Peer Reviewed by two reviewers.
Urinary incontinence (UI) is an embarrassing and distressing adverse effect of antipsychotic agents. Untreated UI may even lead to noncompliance in distressed patients. The incidence of UI and enuresis may be underreported. Although UI associated with antipsychotic use has been recognized, the etiology and optimal treatment strategies have not been fully established. This article was written to review the published literature and to explore the reported treatment options.
Several conventional antipsychotics have been associated with UI, including chlorpromazine, thioridazine, chlorprothixene, thiothixene, trifluoperazine, fluphenazine, fluphenazine (enanthate and decanoate), haloperidol, and pimozide. During the late 1980s, the incidence of clozapine-induced enuresis had been 0.23%. By 2000, many case reports and a few studies had labeled the incidence up to 48%.
A general explanation for the mechanism responsible for antipsychotic-induced UI and enuresis is that these side effects are due to mostly alpha-adrenergic blockade, some dopamine blockade, and a minimum of cholinergic effects on the bladder. Desmopressin seems to be an effective but expensive treatment. There are a myriad of oral treatments including pseudoephedrine, oxybutynin, benztropine, trihexyphenidyl, and dopamine agonists to incorporate with nonpharmacological approaches for UI.
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Guide to Renal/Dialysis Considerations
Joshua Caballero, Pharm.D. and Jennifer L. Potter, Pharm.D.
JCPNP 2002;1(1). Copyright 2002 CPNP. Submitted 6/23/2002; Accepted 8/10/2002; Peer Reviewed by two reviewers.
Over the last several years, there has been an increase in the number of psychotropic medications used in patients with renal disease. Renal dysfunction may lead to an accumulation of drugs and possible toxicity. Therefore, careful monitoring is necessary in order to provide optimal care and decrease potential side effects. Currently, there is not a comprehensive list describing psychotropic medication dosing in renal disease. We have adapted Bennetts guide to drug prescribing in renal failure, used the table as a template, and updated it to include current psychotropic medications. These tables will be beneficial for health care practitioners to appropriately dose patients with renal dysfunction or who are undergoing dialysis.
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Cardiovascular Toxicity with Clozapine Therapy
from Riverview Hospital Pharmacy Newsletter
Volume #22, Issue #6 - June, 2002
Written by: Jenie Le, B.Sc. (Pharm), RCH
Pharmacy Resident
Reviewed by: Debbie Thompson, (Pharm. D)
Clozapine associated myocardial toxicity is rare but potentially fatal. More studies need to be conducted to help determine the actual incidence, possible risk factors and the mechanism of this reaction. -
Urgent Action Required: ASHP DRAFT Specialized Pharmacy Practice Residency Standard
by Larry EreshefskyThe proposed changes mandate a level of training prior to specialty practice residencies which 'requires either an ASHP ACCREDITED pharm practice residency', e.g., could not be a non-accredited one year program; or requires 3 years of experience in lieu of one year residency.
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Ten Year Review of Pharmacist Presentations at NCDEU
by Cara AlfaroThis material was presented to the CPNP members attending the luncheon meeting on May 28, 2001 at the New Clinical Drug Evaluations Unit Meeting of the National Institute of Mental Health at the Arizona Biltmore Hotel in Phoenix. Dr Alfaro reviewed all of the materials that were available to her and extracted the workships and panels that were presented by pharmacists, pharmacists that received New Investigator Awards, and pharmacists that submitted abstracts for Poster Presentations. After Dr. Alfaro's presentation, she led a discussion of potential topics that we could consider proposing for future NCDEU meetings. The next two meetings are scheduled for Boca Raton, Florida.